Outcomes for immuno-chemotherapy based treatment in patients with poorly differentiated extrapulmonary neuroendocrine carcinoma.
Authors: Sakthi Kumar, Toluwalase Talabi, Mahta Mahmoudieh, Daniel Pennington, Kathylynn Saboda, Junaid Arshad, Aaron James Scott
Journal: Journal of Clinical Oncology (2023)

e14619 Background: Extrapulmonary neuroendocrine carcinoma (EP-NEC) represents a rare collection of neuroendocrine cancers characterized with a poor prognosis and modest treatment benefit similar to small cell lung carcinoma (SCLC). Platinum-based chemotherapy (cisplatin or carboplatin) and etoposide is the preferred 1st line therapy for patients (pts) with metastatic EP-NEC who are not eligible for curative surgery (Frizziero et al. 2019). Studies in pts with advanced SCLC have shown improved progression free survival (PFS) and overall survival (OS) with the addition of atezolizumab, an anti-PD-L1 monoclonal antibody, to induction chemotherapy (4 cycles) versus chemotherapy alone (Horn et al. 2018). Prospective trials investigating immune checkpoint inhibitors such as atezolizumab plus chemotherapy have yet to be published in EP-NEC. Methods: We retrospectively reviewed all registered pts at the Gastrointestinal Medical Oncology Clinic at Banner-University of Arizona Cancer Center who received at least 1 dose of atezolizumab from 1/2017 through 3/2022 (UAIRB00001593). Criteria for pt selection for analysis was based on the following: pts diagnosed with grade III, Ki 67&gt;20%, poorly differentiated, metastatic EP-NEC and treated with ≥ 1 dose of atezolizumab plus chemotherapy as 1st line treatment. Results: Ten pts received atezolizumab based therapy during this timeframe. 6 pts met criteria for analysis and 4 pts were excluded for alternative diagnoses. 4 pts were female, 2 pts were male, and the average age at diagnosis was 63.8 years. The median number of chemotherapy cycles was 7.0 [4-17]. The median number of atezolizumab doses was 7.5 [6-28]. The median PFS was 7 months (95% CI 5-*). The median overall survival (mOS) was 13 months (95% CI 8-*). The mOS since starting atezolizumab was 12 months (95% CI 8-*). [*Upper bound of 95% CI cannot be determined.] Five pts (83%) demonstrated a partial response per RECISTv1.1. All pt tumors were MMR-proficient/MSI-stable and PD-L1 expression was negative in 3 pts (PD-L1 status unavailable for 3 pts). No hospitalizations related to immunotherapy or chemotherapy were observed. The most common adverse events included nausea, diarrhea and fatigue. One immune-mediated adverse event of thyroid dysfunction was observed and successfully medically managed. Conclusions: Our experience with atezolizumab plus chemotherapy for 1st line EP-NEC pts demonstrated efficacy via high response rate and survival rates above historical experience. Continuing chemotherapy beyond the induction phase until maximum clinical response demonstrated tolerability with manageable side effects. Although the scope is limited due to sample size, this data supports further investigation of this combination. There is an ongoing large, randomized, prospective trial investigating this regimen in frontline, metastatic EP-NEC pts ( NCT05058651 ).